Adult T-cell Leukemia-lymphoma (ATLL)

Background

• Adult T-cell leukemia lymphoma (ATLL) is an aggressive mature T-cell malignancy caused by the human T-cell lymphotrophic virus (HTLV-1).
• ATLL is divided into 4 subtypes:
  • acute (55%-60% of cases, aggressive)
  • lymphomatous (20% of cases, aggressive)
  • chronic (20% of cases)
  • smoldering (5% of cases, indolent)
• HTLV-1 infection is present in about 5-20 million persons worldwide, and lifetime incidence of ATLL in HTLV-1 carriers in Japan is 3%-5%.
• HTLV-1 transmission by infected lymphocytes may occur via mother to child (especially by breastfeeding), sexual intercourse (mainly male to female), or blood transfusion.

Evaluation

• Suspect adult T-cell leukemia lymphoma (ATLL) in patients from areas with endemic human T-cell lymphotrophic virus (HTLV-1) infection who present with hepatosplenomegaly, lymphadenopathy, hypercalcemia, or skin lesions.
• Routine work-up to establish diagnosis of ATLL includes the following:
  • complete blood count and peripheral blood exam showing ≥ 5% abnormal lymphocytes or "flower" cells
  • serological testing demonstrating antibodies to HTLV-1
  • flow cytometry of peripheral blood or immunohistochemistry in patients having biopsy, showing characteristic abnormal immunophenotype
• The typical immunophenotype for patients with ATLL includes:
  • positive staining for CD2, CD3, CD4, CD5, CD25, CD52, and TCR alpha beta
  • negative staining for CD7 and CD8
• Perform Computed tomography (CT) scan of neck, chest, abdomen, and pelvis to detect extranodal lesions (Strong recommendation).

Management

• Acute adult T-cell leukemia lymphoma (ATLL), the most common form, is associated with poor prognosis and should be treated aggressively. However, the optimal treatment regimen has not been established.
• Consider enrollment in clinical trial as a treatment option for all patients with ATLL (Weak recommendation).
• For management of acute ATLL:
  • Consider zidovudine plus interferon alfa as first-line treatment (Weak recommendation).
  • Consider chemotherapy as an alternative first-line treatment (Weak recommendation).
    • If patient responds after 2 cycles, consider either of:
      • continuing prior therapy (Weak recommendation)
      • allogeneic stem cell transplant (Weak recommendation)
    • If patient does not respond after 2 cycles, consider any of:
      • best supportive care (Weak recommendation)
      • chemotherapy (Weak recommendation)
      • zidovudine plus interferon alfa (Weak recommendation)
    • For patients who respond to any therapy, consider allogeneic stem cell transplant (Weak recommendation).
• For management of lymphomatous ATLL, consider any of:
  • chemotherapy (Weak recommendation)
    • If patient responds after 2 cycles, consider either of:
      • continuing chemotherapy (Weak recommendation)
      • allogeneic stem cell transplant (Weak recommendation)
    • If patient does not respond after 2 cycles, consider either of:
      • best supportive care (Weak recommendation)
      • chemotherapy (Weak recommendation)
    • For patients who respond to any therapy, consider allogeneic stem cell transplant (Weak recommendation).
• For management of chronic or smoldering ATLL, consider:
  • skin-directed therapy in patients with skin lesions (Weak recommendation)
  • observation in asymptomatic or symptomatic patients (Weak recommendation)
  • zidovudine plus interferon alfa in symptomatic patients (Weak recommendation)
    • If patient responds after 2 months of treatment, consider continuing treatment (Weak recommendation).
    • If patient does not respond after 2 months of treatment, consider either of:
      • chemotherapy (Weak recommendation)
      • best supportive care (Weak recommendation)
• Hypercalcemia occurs in about 70% of patients, often accompanied by lytic bone lesions, and should be considered an oncologic emergency requiring prompt treatment; see Hypercalcemia for details.
• Human T-cell lymphotrophic virus (HTLV-1) carriers are typically asymptomatic. Management is focused on prevention of transmission to uninfected individuals by avoiding unprotected sexual contact, avoiding sharing needles, and cessation of breast feeding.
• Screening of pregnant mothers in Japan has been initiated to prevent maternal-infant transmission. Feeding recommendations for HTLV-1 positive mothers includes exclusive formula feeding, freeze-thawing breast milk, or breast feeding < 3 months. No information is available on general screening for populations at high risk for HTLV-1 infection.